This project focusses on the age-related and T-independent properties of polysaccharides, including capsular polysaccharides and detoxified lipopolysaccharides, limit their usefulness (effectiveness) as vaccines for infants, young children and patients with immunologic deficiencies. Synthetic schemes for covalently binding the polysaccharides of pathogenic bacteria to medically useful proteins have been designed to improve the immunologic properties of these protective antigens. Polysaccharide- protein conjugates have been synthesized for pneumococcus type 6B, pneumococcus type 14, the poly alpha-(2->8)-D-NeupNAc the capsular polysaccharide of both Group B meningococcus and Escherichia coli K1, Shigella sp., Haemophilus influenzae type a, Cryptococcus neoformans and Staphylococcus aureus. Evaluation of these conjugate vaccines is at various stages, from laboratory standardization to Phase 3 trials of efficacy. In addition, polyribitol phosphate, a polysaccharide cross- reactive with H. influenzae type b has been isolated and its characterization and use as an addition to the current licensed conjugate vaccines for this pathogen is being evaluated. This work is still in progress.